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The Evil Syndicate was formed when Professor Calamitous stole the plans of an inter dimensional portal through a Flea Bot on Jimmy Neutron's robotic dog pet, Goddard. He used the portal to get access to all worlds and drain their energy with the help of eatch world's villain. In response, Jimmy Neutron assembled eatch world's hero to fight the Syndicate and stop their draining. They passed through Amity Park, Bikini Bottom, and Fairy World until they learned of the Syndicate's true plan: to steal energy from all world's to power up their Doomsday Device which can destroy worlds in a matter of seconds. Once the villains were defeated, Calamitous called them back to attack the heroes all at once. But, even their combined mights could not overcome the heroes and were eventually defeated. The heroes shut down their machine, sending their villains (eatch one trapped somehow) back to their homeworld's.

After Calamitous decided to follow uo other plans for world conquest, another set of villains decided to take over The Syndicate. The new Syndicate was apparently being lead by Technus while the other members were Professor Calamitous's daughter: Beautiful Gorgeous and Pupununu sorceror: Traloc. Plankton kept his position as the only original syndicate member. During the Morphoid invasion, the heroes decided to work together with The Evil Syndicate. Invader Zim and Dib were also willing to help with Dib aiding the Syndicate. The Nicktoons combined might along with The Vessel of Portencia was enough to stun the morphoid leader: Globulous Maximus. However, the villains kick all the heroes out of the Vessel, planning to use Globulous to their own evil ends. Globulous however, switches sides and destroys the Vessel, leaving the villains drifting in space.